A. Although the effects of age on the cardiac response to maximal aerobic exercise are well known in men, whether women undergo similar aging changes is unknown. To determine the independent effects of age and gender on the left ventricular response to exercise, we performed gating blood pool scans at rest and maximal upright cycle exercise in 121 men and 79 women ages 22-86 yrs free of heart disease by history, physical exam, rest and exercise ECG and if greater than 40 yr old, exercise thallium scan. Maximal cycle workload declined similarly with age in men (36%) and women (42%) between the third and ninth decades, although the absolute maximal load achieved was higher in men for any given age. At seated rest age-associated declines in heart rate (HR) and increases in systolic blood pressure (SBP) were observed in both sexes. Resting end-diastolic volume index (EDVI) and stroke volume index (SVI) rose with age in men but not in women. In both sexes, maximal heart rate, ejection fraction and cardiac index declined with age whereas end systolic volume index (ESVI) and total systemic vascular resistance (TSVR) increased. Although EDVI at maximal effort increased with age in men but not in women, SVI was not age related in either sex. Thus, aging and gender have distinct influences on the cardiac response to maximal cycle exercise. B. The response to strenuous aerobic exercise (EX) is mediated in large part by beta- adrenergic activation, the efficiency of which declines with advancing age. To ascertain the importance of the beta-adrenergic system on age- associated changes in hemodynamic during EX, we performed maximal cycle EX in 25 healthy men ages 28-72 yr from the BLSA after acute beta blockade with intravenous propranolol. In these men, EDVI at peak workload declined with age (r= - 0.45) causing an age-associated decline in SVI (r= 0.48, p less than 0.05) not present in 70 unblocked men. The decline in HR with age in propranolol-treated men was blunted (0.46 beats/min/yr) compared to controls (1.09 beats/min/yr). Maximal LVEF declined with age similarly with (r= -0.50, p less than .01) and without (r= -0.45, p less than .0001) beta-adrenergic blockade. The primary reason for the slope shifts in the age regressions propranolol was a large increase in EDVI and SVI and a large decrease in HR in younger men. Similarly, IV propranolol resulted in reduced peak filling rates with EX in young (27 +/- 8 yr) but not older (62 +/- 6 yr) men relative to their unmedicated age peers. We conclude that age differences in beta-adrenergic responsiveness underlie many of the age- associated changes in hemodynamic during vigorous aerobic EX.